The thrust of the program is the synthesis of compounds which are known or have potential as antitumor/antiviral agents with appropriate followup biological screening. The overall objectives are: (i) Development of efficient methods for the synthesis of several unusual, naturally occurring nucleosides analogues which have antitumor and/or antiviral activity. (ii) Synthesis and screening of novel nucleoside analogues designed as possible antitumor/antiviral agents by analogy with known bioactive substances or on the basis of known or probable enzymatic pathways. (iii) Synthesis and screening for antitumor activity of a variety of analogues of prostanoids and prostanoids metabolites. (iv) Development of efficient methods for the production of optically pure starting materials, particularly dialkoxycyclopentenones, which should be widely useful in enantiospecific syntheses of a variety of bioactive substances. (v) Development of new synthetic methods of general interest for organic synthesis. (vi) Further demonstration of the applicability of the materials and methods developed by synthesis of a selection of additional targets of biological interest. Targets of priority include carbocylic nucleoside analogues based on the carbocycle of neplanocin A, novel nucleosides designed to be inhibitors of methyltransferases, novel variations of the chain terminator nucleosides drugs azidothymidine and dideoxycytodine of current interest in AIDS therapy, the recently discovered antiviral nucleoside oxetanocin and a variety of electrophilic cyclopentenones related to prostanoids and designed to serve as DNA polymerase inhibitors.